Oligodendrocyte Injury Is an Early Event in Lesions of Multiple Sclerosis

The ultrastructural features of 11 stereotaxic brain biopsy specimens that demonstrated inflammatory primary demyelination consistent with acute multiple sclerosis were examined. Uniform widening of inner myelin lamellae (biphasic myelinopathy) and degeneration of inner glial loops (“dying-back” oligodendrogliopathy) were early pathologic abnormalities that antedated complete destruction of myelin sheaths. Perivascular inflammatory cells (lymphocytes, macrophages, and occasional plasma cells) were in intimate contact with degenerating myelin sheaths. The response of astrocytes was prominent, even in areas of minimal demyelination. Oligodendrocytes were morphologically preserved in early lesions but proliferated at the periphery of active lesions. Thinly myelinated axons indicative of central nervous system-type remyelination by oligodendrocytes were observed primarily at the edge of plaques. Disturbances of the myelinating function of oligodendrocytes—unaccompanied by death of these cells—may be among the earliest pathologic features in multiple sclerosis.